This application is a renewal of an ongoing project to understand mitotic or cell division defects in cancer. Our goals are to identify the source of the defects and their impact on oncogenesis. Within this broad category, the project will focus on the source of centrosome amplification and polyploidy. This is a newly emerging area of cancer biology and the mechanisms are poorly understood. Both cancer and normal cells grown in culture will be investigated. We have shown that cancer cells often fail to divide properly because of defects in regulatory myosin light chain phosphorylation. We believe that this is due to inhibition of the kinase responsible for adding the phosphate to the myosin light chain. We propose to determine how this kinase is inhibited in tumor cells. If the mistakes in division are understood, we might be able to prevent the abnormal proliferation of cells in tumors. PUBLIC HEALTH RELEVANCE: Cancer is found in more than 1.4 million Americans each year and kills almost 600,000. This study examines the cellular defects that result in cancer cells having genetic instability that ultimately results in cancer spread and resistance to therapy. The results of this study may lead to new prognostic tests and better therapies for this deadly disease.